First Author | Ma J | Year | 2014 |
Journal | J Leukoc Biol | Volume | 95 |
Issue | 2 | Pages | 275-83 |
PubMed ID | 24082012 | Mgi Jnum | J:209537 |
Mgi Id | MGI:5568046 | Doi | 10.1189/jlb.0513297 |
Citation | Ma J, et al. (2014) Differential role of all-trans retinoic acid in promoting the development of CD4+ and CD8+ regulatory T cells. J Leukoc Biol 95(2):275-83 |
abstractText | It is known that ATRA promotes the development of TGF-beta-induced CD4(+)Foxp3(+) iTregs, which play a vital role in the prevention of autoimmune diseases; however, the role of ATRA in facilitating the differentiation and function of CD8(+)Foxp3(+) iTregs remains elusive. Using a head-to-head comparison, we found that ATRA promoted expression of Foxp3 and development of CD4(+) iTregs, but it did not promote Foxp3 expression on CD8(+) cells. Using a standard in vitro assay, we demonstrated that CD8(+) iTregs induced by TGF-beta and ATRA were not superior to CD8(+) iTregs induced by TGF-beta alone. In cGVHD, in a typical lupus syndrome model where DBA2 spleen cells were transferred to DBA2xC57BL/6 F1 mice, we observed that both CD8(+) iTregs induced by TGF-beta and ATRA and those induced by TGF-beta alone had similar therapeutic effects. ATRA did not boost but, conversely, impaired the differentiation and function of human CD8(+) iTregs. CD8(+) cells expressed the ATRA receptor RAR and responded to ATRA, similar to CD4(+) cells. We have identified the differential role of ATRA in promoting Foxp3(+) Tregs in CD4(+) and CD8(+) cell populations. These results will help to determine a protocol for developing different Treg cell populations and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation. |